This invention relates to a highly purified human lymphokine and, more particularly, to a lymphocyte factor which regulates antibody responses known as soluble immune response suppressor (SIRS).
Several nonspecific suppressor factors have been reported that are released by sensitized lymph node or spleen cells after challenge with the specific antigen or by spleen cells inoculated with Concanavalin A (Con A). One of these factors has been designated soluble immune response suppressor (SIRS). Rich and Pierce, J. Immunol. 112(4), 1360-1368 (1974). It is an early product of mouse spleen cells (Ly2, 3.sup.+ T cells) stimulated with antigen or Con A. In appropriate dilutions, it nonspecifically suppresses 5-day plaque-forming cell (PFC) responses to sheep red blood cells (SRBC) as well as antihapten antibody responses.
SIRS is known to be activated by macrophages or exogenous H.sub.2 O.sub.2 to SIRS.sub.ox, a reaction which is inhibited by catalase, levamisole and electron donors such as 2-mercaptoethanol (2-ME).
For further background information on the murine-derived SIRS, see the recent review article by Aune and Pierce, J. Immunol. Methods 53, 1-14 (1982); and their review paper in Lymphokines, Vol. 9, Ed. E. Pick, Academic Press, Inc., New York, 1984, pp. 257-277.
Recently, the purification and characterization of two molecular forms of murine SIRS having molecular weights of 21,500 and 14,000, respectively, was reported by Aune et al., J. lmmunol. 131 (6), 2848-2852 (1983). Isoforms of SIRS with molecular weight of 11,000 are also disclosed by Webb et al., J. Immunol. 135, 3238 (1985), and in a U.S. patent application filed by Pierce and Webb, Oct. 22, 1985, Ser. No. 789,997, and jointly owned by a common assignee of the present application.
Human counterparts of murine SIRS also are known. See, for example, Schnaper, Pierce and Aune, J. Immunol. 132 (5), 2429-2435 (1984), which identifies the human factors as having 110,000-160,000 molecular weight when fractionated by chromatography on Sephacryl.RTM. S-200 gel using buffers of physiologic ionic strength, but suggests that fractionation in high ionic strength buffers may reduce the apparent molecular weight as in the case of murine SIRS.
In copending application Ser. No. 653,123, filed Sept. 21, 1984, now U.S. Pat. No. 4,665,021, a molecular weight of 10,000-15,000 is assigned to the latter fractionated human SIRS. According to the disclosure in said application, SIRS can also be fractionated from human urine samples of nephrotic patients, whereby its presence can serve as a useful diagnostic tool for screening for immune deficiency. See also Schnaper and Aune, J. Clin. Invest. 76, 341 (1985).
The specificity of assays for SIRS has been enhanced recently by utilization of monoclonal anti-murine SIRS antibodies which cross-react with human SIRS, and the identification of a characteristic elution pattern for human SIRS on high performance liquid chromatography (HPLC). See Aune, J. Immunol. Meth. 8, 33(1985).